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STANFORD, CA—As we stood in front of the mirror brushing our teeth a few weeks ago, my friends agreed that smoking cigarettes is bad. The Center for Disease Control, the American Lung Association, and anyone with an internet connection and a brain tend to agree on this one.[1] The irrefutable toxicity, the nefarious campaigns of the tobacco industry, the outlandish anti-smoking commercials we cringed at as children—to our demographic, at least, the point has been made. Cigarettes=cancer=death.

But marijuana is a different story. Californians recently voted “yes” on Proposition 64, the state’s second attempt to legalize recreational marijuana for adults 21+.[2] Before the vote, I began to wonder if they had the information to make a scientifically informed choice. As I scrubbed my canines, my friends concluded weed isn’t that bad for you because it doesn’t contain tar and is an unprocessed, natural plant product.

How do they know that? I thought. When was the last time any of us read a scientific paper on the physiology of marijuana?

“Weed Science” Survey. Posted as a Google Form to Stanford ’19 Facebook Group. Live 10/31/16-11/4/16. [3]

Unfortunately, as I soon discovered, being an informed consumer in the marijuana market is actually really hard. Variability in both medical opinion and quality of research made it challenging for me to digest what Stanford’s plethora of databases, journals, and archives churned up.

As I plunged into this ambiguous body of weed research, I kept some questions in mind: What is the drug mechanism? Does weed, like tobacco, give you cancer? How do the chemicals in marijuana affect the brain? After preliminary research, I created a survey to plumb my peers’ knowledge about weed. 99 members of Stanford’s Class of 2019 completed the survey. They averaged 2.56 out of 5 true/false questions, with a median score of 2.[3] Could you do better? Fasten your seatbelt—you’re about to find out.

HOW IT WORKS

Faced with a seemingly infinite span of research papers and op-eds, I started my investigation from square one: how does marijuana produce a high?

It turns out that for all the wondrous, mind-altering effects it yields, the chemical THC (also known as ∆9-tetrahydrocannabinol) is not magical. The body already has a system in place to deal with similar chemicals, called cannabinoids. These cannabinoids, along with enzymes that synthesize and degrade them and receptors they stimulate, make up the Endocannabinoid System.[4] THC isn’t produced by the body, but it is still a cannabinoid and can therefore activate or inhibit these pathways, changing how the brain processes information.[5]

Though widespread marijuana culture raises a lot of scientific interest in the Endocannabinoid System, only two receptors are well understood—there are probably three or four more. These receptors, CB1 and CB2, make up distinct pathways that have different physiological effects.[6]

CB1 receptors are abundant on neurons throughout the brain, but are also present at lower concentrations on neurons in other organs and tissues.[5] The natural cannabinoids within the body interact with CB1 to protect the Central Nervous System from over-stimulation or over-inhibition by neurotransmitters. Chemical interactions of THC with CB1 yield the psychoactive effects of marijuana.[6]

CB2 receptors have lower overall concentrations, but are also present in the brain and cells of the immune system. Activity at CB2 increases a hundred fold after a tissue injury or as an inflammatory response occurs. CB2 plays a role in immune system regulation and white blood cell release.[5,7]

THC from marijuana interacts with each of these receptors, but because it’s not natural to the body, it creates all sorts of funky effects, which include but are not limited to its psychoactive effects.

As soon as you inhale, your airway and lungs are the first tissues exposed. What ensues before THC even reaches your brain?

WEED, LUNGS, AND CANCER

Setting drugs on fire is a tried-and-true practice to get them into the body. In the case of marijuana, the heat of the cannabis combusting vaporizes THC, which is inhaled as a cloud of distinctly-scented smoke.

Apparently, the belief that this smoke is nontoxic, especially compared to cigarette smoke, is pervasive. 80 out of 99 Stanford students who chose to complete my survey agreed with my friends that “smoking marijuana is healthier than smoking tobacco because marijuana doesn’t contain tar.”[3]

Unfortunately, they are incorrect. The combustion reaction by which marijuana is smoked also produces over a hundred other toxic compounds, including tar and a plethora of known carcinogens.[6,7] But despite its toxicity, and despite the best efforts of some research groups, scientific literature does not support a correlation between heavy marijuana use and lung or upper airway cancers. Nor does it support a connection between chronic obstructive pulmonary disease (COPD) and marijuana smoking.[7] By contrast, the fact that tobacco use dramatically increases risk of cancer and COPD is supported by overwhelming scientific and statistical evidence.[1,9]

Cannabis Consumption. Image courtesy of Ashton. [18]

So what’s the difference, if both substances produce toxic smoke? It seems that the quantity of material smoked by a heavy user is what gives tobacco such devastating health effects as compared to marijuana. Pack-a-day cigarette smokers use about 20 grams of tobacco per day to the pothead’s 4 grams of weed.[6,7]

Now, the fact that smoking lots of weed is unlikely to directly cause fatal heart disease or cancer does not mean inhaling toxic smoke has no adverse effects. Frequent use causes chronic bronchitis and non-acute respiratory unpleasantness—marijuana smokers inhale more deeply than tobacco smokers, damaging the linings of the lungs and inhibiting the ability to clear mucus.[10]

The respiratory system is also affected by THC’s interactions with receptors in the lungs. At CB1 receptors, THC blocks the neurotransmitters that cause muscles to constrict in response to the smoke—THC actually relaxes the airway and bronchioles rather than tightening them. At CB2, THC disrupts the inflammatory and immune responses, making the lungs more vulnerable to infections. Accumulating phlegm and a dampened immune response naturally lead to persistent bronchitis symptoms for heavy smokers.[7]

Although these effects are not acute for healthy people, they can cause lifestyle changes for chronic or heavy users. Slimy, infected lungs make exercising hard, even for a young person. For people who are older or immunocompromised, these effects can become serious health problems, especially in combination with heart disease.[11,12]

Okay, bronchitis isn’t ideal. But if what I’m saying is that weed won’t give you cancer, doesn’t that mean my friends were right after all to say marijuana is comparably healthier?

Researchers and physicians around the world cringe at the very thought. Like many real-life public health issues, it’s just not that simple. Cigarettes and marijuana are two very different cases. Perhaps we ought to reconsider if cancer risk is the appropriate litmus by which we judge the “healthiness” of marijuana.

THE SMOKING SECTION

The modern understanding of how cigarette smoking affects the body is truly impressive. This is not only because we have nearly a century and a half worth of literature on the topic, but also because cigarettes are so extremely poisonous that the evidence all but fell from the sky. We just don’t know as much about marijuana, and its effects seem to be subtler. This has caused many to unwisely dismiss it as innocuous.

Again, most people with a brain and an internet connection can be convinced that smoking cigarettes is terrible for you.

“Tobacco now kills about six million people every year, more than AIDS, malaria, and traffic accidents combined.” –The Golden Holocaust, Robert Proctor[9]

The tome quoted above is a 700-page, excruciatingly-researched rant about the nefarious tobacco industry. Robert Proctor chose the title The Golden Holocaust because of the unfathomable death toll the industry incurred by covering up the danger of cigarettes to protect itself. Evidence of the toxicity of cigarettes goes all the way back to the 19th century. The Germans knew nicotine was poisonous by the 1820s. By the early 20th century, physicians began to suspect a connection between cigarettes and lung cancer when lung cancer rates skyrocketed in the wake of a flourishing tobacco industry.[9]

It was fairly logical for physicians in the early 20th century to link the rise of the tobacco industry with the rise of lung cancer; all they had to do was document how many of their lung cancer patients also happened to be cigarette smokers. (Spoiler alert: most of them.)

Studies like this which link a population to an epidemic are known as epidemiological studies. Though they are useful for helping scientists identify the major forces at play within a population surrounding a particular malady, they are only correlative and do not imply causation. Hundreds if not thousands of scientific studies have supported the tobacco equals death hypothesis, providing us with hard statistics and a wealth of information on how exactly smoking cigarettes ravages the human body.

The effects of chronic marijuana smoking are not overwhelmingly lethal. But interpreting a more nuanced physiological response to mean marijuana is healthier than cigarettes is patently foolish—there’s still so much we don’t know about the long-term effects of chronic use.

The physiological nightmare that is tobacco smoking. Image courtesy of Mikael Häggström. [13]

If not cancer, then what are we so worried about? Let me take you back to the Endocannabinoid System one last time. What we don’t know about it may not kill us, but it will cause a lot of grief.

POTHEAD

Almost 85 percent of the students I polled agreed that “smoking marijuana heavily during adolescence causes abnormalities in the structure of and connectivity within the brain.” 10 out of the 11 students who reported smoking marijuana pretty much every day got this question right. Interesting.[3]

Research supports significant changes in brain activity for heavy users. This makes some intuitive sense—we know that THC meddles with the Endocannabinoid System, whose functions include moderating neurological processes. Though we again run into the issue of causality for epidemiological studies, brain imaging of adults who smoked marijuana heavily as adolescents demonstrate a variety of abnormalities from decreased connectivity within certain regions to reduced hippocampus volume.[11]

But what concerns pediatricians most about marijuana dependence are its negative psychosocial and long-term cognitive impacts. I spoke to Dr. Seth Ammerman, a clinical professor in the department of pediatrics at Stanford School of Medicine, about the gaps in our understanding of marijuana’s effects on adolescence.

He emphasized that though our scientific understanding of marijuana’s effects on brain development is lacking, we already have enough epidemiological information to be worried about adolescents at risk for addiction. Studies have shown rather conclusively (I asked him again to be sure) that regular, heavy, or daily marijuana users have more psychosocial and cognitive problems. That is, they do worse in school, are more likely to drop out, and struggle to hold jobs.

Though marijuana is addictive for about 1 in 10 adults and 1 in 6 teens[6,11], Ammerman pointed out that in contrast to other drugs like heroin, marijuana addiction is usually not lifelong. This is undeniably a good thing, but there’s a caveat. “If you take a mid-teen, say a 17-year-old, who has developed a marijuana use disorder, often ten years later he or she no longer would be diagnosed with it,” remarked Dr. Ammerman. “But those ten years have not gone well.”

Marijuana use reported by 99 Stanford sophomores (Brakebill).

Again, losing time doesn’t seem on the outset to be as devastating as getting cancer from cigarettes. But consider a young person who becomes dependent on weed and within those ten years drops out of high school, ruins his or her credit, and functions poorly in society. Those ten years aren’t just time—they’re opportunity. Losing the chance get a high school or college degree and start building a stable and productive life is absolutely devastating. To the populations who are most at risk—the kids from low-resource families whose parents don’t have the bandwidth to keep them from developing a drug habit—years lost to marijuana dependence could take away their social mobility.

Dr. Ammerman and the rest of the American Academy of Pediatrics (AAP) opposed legalization efforts in the state of California for a number of reasons. Their primary focus, however, was to postpone adolescent use of marijuana until the “cut-point” of brain development at around 18 after which risk of developing a use disorder decreases.[14]

Another motive for the AAP to oppose legalization was to stall for time in hopes of better research. Marijuana is classified as a Schedule I drug (along with heroin) under the Controlled Substances Act.[6] Scheduling hypothetically has to do with the medical usefulness, but is actually quite political. Marijuana’s scheduling status makes it near-impossible to study—scientists must push through three different bureaucracies in order to be approved.[15]

Moving marijuana to Schedule II would enable researchers to study it, but this change must be approved by Congress or the Attorney General. Ammerman and I heaved a deep sigh for the fate of our nation. “Congress is highly dysfunctional right now,” he remarked.[15] And less than a week later, marijuana was legalized in California.

THE BRAVE NEW WORLD

Welcome to America, where marijuana is legalized in more states each year,[19] and where our unparalleled capacity to research it will likely go untapped for at least another four years. We know enough to be concerned for the adolescent brain in instances of heavy use, but that’s about it. Our prospective Attorney General, Alabama Senator Jeff Sessions, believes that “good people don’t smoke marijuana.”[16] He is far more likely to continue Reagan’s War on Drugs than move marijuana to Schedule II.

There are some encouraging statistics. Surveys from Colorado over the past several years don’t show increased use, which Dr. Ammerman thought was a good sign that maybe legalization won’t be as harmful as the AAP fears.[15]

But what concerns me most is how hard it was to write this article. I dedicated many hours and wielded the full force of Stanford University’s library resources looking into marijuana physiology. And I still had a difficult time synthesizing what I found and understanding the highly controversial and politicized world of marijuana research.

If I end this project better informed but still uncertain, how can millions of young people with fewer resources be expected to make informed decisions about marijuana use?

In this brave new world, smoking marijuana is the individual’s prerogative. We have to demand a cohesive interpretation of the current scientific understanding of marijuana from the government and the medical field. Maybe Trump’s Congress can be pressured into a scheduling change. Maybe they can work with communities to teach kids what we know and what we don’t.

But maybe we should just give up on the government altogether, print millions of copies of this article, and disperse them to enlighten the masses.

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Fascinate is an online science publication run by undergraduate students at Stanford that focuses on communicating exciting scientific innovations in the fields of biology, physical sciences, health, technology, and more to the general public.